Develop a Deep-Learning Model to Predict Cancer Immunotherapy Response Using In-Born Genomes
Bibliographic record
Abstract
The emergence of immune checkpoint inhibitors (ICIs) has significantly advanced cancer treatment. However, only 15-30% of the cancer patients respond to ICI treatment, which stimulates and enhances host immunity to eliminate tumor cells. ICI treatment is very expensive and has potential adverse reactions; therefore, it is crucial to develop a method which enables to accurately and rapidly assess a patient's suitability before ICI treatment. We complied germline whole-genome sequencing (WES) data of 37 melanoma patients who have been treated with ICIs and sequenced in our lab previously, and the WES data of other 700 ICI-treated cancer patients in public domain. Using these data, we proposed a novel double-channel attention neural network (DANN) model to predict cancer ICI-response and validate the predictions. DANN achieved a mean accuracy and AUC of 0.95 and 0.98, respectively, which outperformed traditional machine learning methods. Enrichment analysis of the DANN-identified genes indicated that cancer patients whose in-born genomic variants might mainly affect host immune system in a wide-ranging manner, and then affect ICI response. Finally, we found a set of 12 genes bearing genomic variants were significantly associated with cancer patient survivals after ICI treatment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".